DESCRIPTION (Applicant's Description) This application for renewal of the University of Virginia Cancer Center Support Grant continues the development of the Cancer Center from a Basic to a Clinical Center. It builds on and expands the original strengths in basic science research while demonstrating the ability to translate that strength into investigations with increased cancer focus and clinical interactions. In addition, it demonstrates substantial movement toward the achievement of Comprehensive status. The Cancer Center Support Grant has been organized into six Programs, five of them laboratory based and one Clinical program. The Laboratory Programs represent investigational disciplines that address fundamental problems in cancer cell and molecular biology. The Clinical Program serves as an incubator for the establishment of multi-disciplinary "working groups" focused on a specific disease or approach to the treatment, diagnosis or prevention of cancer. Program A.1, Cell Signaling focuses on molecular mechanisms of intracellular regulation including oncogenes, receptors, intracellular signal transduction, gene regulation and DNA replication, which are key to understanding normal and malignant growth. Program A.2, Endocrinology focuses on growth, differentiation and regulation of endocrine cells. This Program has a distinguished record of clinical, translational and fundamental research and has increased its cancer focus, with an emphasis on breast cancer. Program A.3, Immunology has great strengths in the areas of T-cell activation, antigen presentation and immune surveillance, issues which are of fundamental and practical importance in cancer immunology. Program A.4, Metastasis and Invasion is built on existing basic science strengths in membranes, extracellular matrices, proteases, vascular development and cell motility which will be brought to bear on the important problems of tumor invasion and metastasis. Program A.5, Structural Biology is a new Program. It brings an already strong structural biology research group under the Cancer Center umbrella and has started to make major contributions to fundamental cancer-related problems. Program B.1, Clinical Oncology is designed to provide the clinical venue for interactions with the five laboratory-based Programs. Its goal is to identify cellular or immunologic targets for therapy or diagnosis; develop drugs or biologicals to attack that target; and test these drugs or biologicals in the clinical setting. This process is facilitated by the formation of inter-disciplinary "working groups" with individuals drawn from each stage of the development process. The research activities of the Cancer Center are supported by nine laboratory-based shared facilities (Biomolecular, Electron Microscope, FACS, Hybridoma, Transgenic, Tissue Procurement, Tissue Culture, Research Histology, Small Animal Imaging) a Biostatistics Core and a Clinical Trials office. These research cores support fundamental cancer research and facilitate the movement of ideas and technologies between the laboratory and the clinic.